Optimized 'inverse activation' methodology for esterification of hydroxyl-functionalized resins

Since the advent of the solid-phase method for peptide synthesis, the esterification of protected amino acid derivatives onto hydroxyl-functionalized resins has been problematic on many levels. Most methods for this reaction are attended by unacceptable levels of racemization and/or dipeptide formation, or require the use of expensive reagents with difficult handling properties. Herein, we describe a straightforward, generally-applicable method for the esterification of hydroxyl-functionalized resins, in high yield and complete stereochemical integrity.

A generally-applicable methodology for high-yielding, racemization-free esterification of Fmoc amino acids onto hydroxyl-functionalized resins is described.